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Older African-Americans, a rapidly growing segment of the U.S. population, bear a disproportionate burden of Alzheimer’s disease and cognitive impairment compared to non-Hispanic whites, with some estimates suggesting that they may have more than a two-fold increased risk than their white counterparts. Recent studies have led to significant advances in our understanding of the underlying neurobiologic substrates of Alzheimer’s disease. But because of challenges in the recruitment of African-Americans into research studies and an unfortunate lack of clinical and biologic data in this population, knowledge of the drivers of the disparities has lagged behind. The ability to identify therapeutic targets and effective interventions for this population has become a public-health imperative. In this lecture, Dr. Barnes will present data from several longitudinal cohort studies of older African-Americans on how risk factors and resilience markers impact cognitive aging. She will also discuss preliminary data on racial differences in brain pathology measured at death. The data may lead to opportunities in identifying new mechanisms and new knowledge for Alzheimer’s disease, cognitive impairment, and cognitive decline.